Cancer Science Online Publication: Phase II Data Demonstrated Clinical Safety and Efficacy of First-in-Class Small Molecule Icaritin in Patients with Advanced HBV-related Hepatocellular Carcinoma
Congratulations to team investigators and ShenogenPharma teams. Cancer Science has published ourphase II trial data titled “Icaritin Induced Immunomodulatory Efficacy inAdvanced HBV-Related Hepatocellular Carcinoma: Immunodynamic Biomarkers andOverall Survival"(http://dx.doi.org/10.1111/cas.14641).This phase II trial was led by prestigiousclinical investigators of professor Yan Sun and Professor Qin Shukui, alongwith multiple clinical research centers in China. Icaritin is a novel small molecule drugproduced by enzymatic hydrolysis of the extract isolated from the traditionalChinese herbal medicine Epimedium.
Advanced stages of patients withhepatocellular carcinoma (HCC) in China are mostly (about 85%) related tohepatitis B virus (HBV) infection, usually accompanied by a high-risk of mixeddiseases such as chronic inflammation, liver damage, immune tolerance orabnormalities, and poor prognosis compared to non-HBV infected cases. Unfortunately,there is lack of optimal treatment options for these patients, often due to drugtoxicity, limited liver tolerability, and uncertainty of safety and efficacy ofusing current treatment regimen including sorafenib.
First-in-class Icaritin, a novel immunomodulatorysmall molecule was applied in a single arm, multi-centered phase II trial in 68patients with advanced hepatocellular carcinoma (with 91.2% HBV infection).Study showed the superior safety profileover the traditional targeted treatment (i.e. sorafenib) and immune checkpointinhibitors (i.e. anti-PD-1). No grade 3/4 adverse events were observed, but withsignificant anti-inflammatory and antitumor immunomodulatory efficacy. Icaritin-treatedpatients with dynamic changes of immune biomarkers showed significant survival improvement(mOS 329-565days). The composite biomarkers of advanced hepatocellularcarcinoma (HCC) patients with poor prognosis including high expression AFP and Tcell (Th1) cytokines showed significant survival improvement after icaritin treatment.This might be particularly encouraging for those advanced HCC patients with poorprognosis or with high-risk HBV-related liver dysfunction and immune disorders.
Icaritin phase III trial is actively ongoing.With its unique mechanism of action (MOA) including anti-inflammatory, antitumorimmunomodulation via NF-kB and IL-6/JAK2/STAT3pathways and advantages of clinical safety, oral treatment and easy access, itis reasonable to expect icaritin to be a novel alternative small molecule-basedimmune therapy to treat advanced HCC patients including those with poorprognosis, HBV infection, liver dysfunction and immune abnormalities, particularlyin Asia countries and low-income regions and to reduce the mortality.